tbuckley/cabot-search huggingface dataset:
Progress Toward Measles Elimination — African Region, 2017–2021
Authors: Balcha G. Masresha, Cynthia Hatcher, Emmaculate Lebo, Patricia Tanifum, Ado M. Bwaka, Anna A. Minta, Sebastien Antoni, Gavin B. Grant, Robert T. Perry, Patrick O’Connor
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Worldwide, measles remains a major cause of disease and death; the highest incidence is in the World Health Organization African Region (AFR). In 2011, the 46 AFR member states established a goal of regional measles elimination by 2020; this report describes progress during 2017-2021. Regional coverage with a first dose of measles-containing vaccine (MCV) decreased from 70% in 2017 to 68% in 2021, and the number of countries with ≥95% coverage decreased from six (13%) to two (4%). The number of countries providing a second MCV dose increased from 27 (57%) to 38 (81%), and second-dose coverage increased from 25% to 41%. Approximately 341 million persons were vaccinated in supplementary immunization activities, and an estimated 4.5 million deaths were averted by vaccination. However, the number of countries meeting measles surveillance performance indicators declined from 26 (62%) to nine (22%). Measles incidence increased from 69.2 per 1 million population in 2017 to 81.9 in 2021. The number of estimated annual measles cases and deaths increased 22% and 8%, respectively. By December 2021, no country in AFR had received verification of measles elimination. To achieve a renewed regional goal of measles elimination in at least 80% of countries by 2030, intensified efforts are needed to recover and surpass levels of surveillance performance and coverage with 2 MCV doses achieved before the COVID-19 pandemic.
Health Care Provider Knowledge and Attitudes Regarding Adult Pneumococcal Conjugate Vaccine Recommendations — United States, September 28–October 10, 2022
Authors: Rebecca Kahn, Lindsay Zielinski, Amber Gedlinske, Natoshia M. Askelson, Christine Petersen, Andrew M. Parker, Courtney A. Gidengil, Alison P. Albert, Angela J. Jiles, Megan C. Lindley, Miwako Kobayashi, Aaron M. Scherer
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Despite the availability of effective vaccines against pneumococcal disease, pneumococcus is a common bacterial cause of pneumonia, causing approximately 100,000 hospitalizations among U.S. adults per year. In addition, approximately 30,000 invasive pneumococcal disease (IPD) cases and 3,000 IPD deaths occur among U.S. adults each year. Previous health care provider surveys identified gaps in provider knowledge about and understanding of the adult pneumococcal vaccine recommendations, and pneumococcal vaccine coverage remains suboptimal. To assess the feasibility and acceptability domains of the Advisory Committee on Immunization Practices (ACIP) Evidence to Recommendations (EtR) framework, a health care provider knowledge and attitudes survey was conducted during September 28-October 10, 2022, by the Healthcare and Public Perceptions of Immunizations Survey Collaborative before the October 2022 ACIP meeting. Among 751 provider respondents, two thirds agreed or strongly agreed with the policy option under consideration to expand the recommendations for the new 20-valent pneumococcal conjugate vaccine (PCV20) to adults who had only received the previously recommended 13-valent pneumococcal conjugate vaccine (PCV13). Gaps in providers' knowledge and perceived challenges to implementing recommendations were identified and were included in ACIP's EtR framework discussions in late October 2022 when ACIP updated the recommendations for PCV20 use in adults. Currently, use of PCV20 is recommended for certain adults who have previously received PCV13, in addition to those who have never received a pneumococcal conjugate vaccine. The survey findings indicate a need to increase provider awareness and implementation of pneumococcal vaccination recommendations and to provide tools to assist with patient-specific vaccination guidance. Resources available to address the challenges to implementing pneumococcal vaccination recommendations include the PneumoRecs VaxAdvisor mobile app and other CDC-developed tools, including summary documents and overviews of vaccination schedules and CDC's strategic framework to increase confidence in vaccines and reduce vaccine-preventable diseases, Vaccinate with Confidence.
<i>QuickStats:</i> Number of Deaths Resulting from Being Bitten or Struck by a Dog,* by Sex — National Vital Statistics System, United States, 2011–2021
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Male Female* Deaths from being bitten or struck by a dog as underlying cause of death were coded as W54, according to the International Classification of Diseases, Tenth Revision, and exclude deaths from rabies resulting from a dog bite.During 2011-2021, a total of 468 deaths from being bitten or struck by a dog occurred (average = 43 deaths per year).The annual number of deaths ranged from 31 (2016) to 81 (2021).During 2011-2016, more deaths occurred among males than among females during most years; however, during 2017-2021, more deaths occurred among females than among males.From 2018 to 2021, deaths more than doubled for both males (from 15 to 37) and females (from 20 to 44).
FDA Approval Summary: Tremelimumab in Combination with Durvalumab for the Treatment of Patients with Unresectable Hepatocellular Carcinoma
Authors: Timil H. Patel, Jamie R. Brewer, Jiaxin Fan, Joyce Cheng, Yuan-Li Shen, Yue Xiang, Hong Zhao, Steven J. Lemery, Richard Pazdur, Paul G. Kluetz, Lola A. Fashoyin-Aje
Journal: Clinical Cancer Research (2023)

On October 21, 2022, the FDA approved tremelimumab (Imjudo) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma. The approval was based on the results from the HIMALAYA study, in which patients with unresectable hepatocellular carcinoma who were naïve to previous systemic treatment were randomly assigned to receive one of three study arms: tremelimumab in combination with durvalumab (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The primary objective of improvement in overall survival (OS) for tremelimumab in combination with durvalumab compared with sorafenib met statistical significance with a stratified HR of 0.78 [95% confidence interval (CI), 0.66-0.92; P = 0.0035]. The median OS was 16.4 months (95% CI, 14.2-19.6) with tremelimumab in combination with durvalumab and 13.8 months (95% CI, 12.3-16.1) with sorafenib. Adverse reactions occurring in ≥20% of patients receiving tremelimumab in combination with durvalumab were rash, fatigue, diarrhea, pruritus, musculoskeletal pain, and abdominal pain. The recommended tremelimumab dose for patients weighing 30 kg or more is 300 mg, i.v., as a single dose in combination with durvalumab 1,500 mg at cycle 1/day 1, followed by durvalumab 1,500 mg, i.v., every 4 weeks. For those weighing less than 30 kg, the recommended tremelimumab dose is 4 mg/kg, i.v., as a single dose in combination with durvalumab 20 mg/kg, i.v., followed by durvalumab 20 mg/kg, i.v., every 4 weeks.
ADAMTS-7 Modulates Atherosclerotic Plaque Formation by Degradation of TIMP-1
Authors: M. Amin Sharifi, Michael Wierer, Tan An Dang, Jelena Milic, Aldo Moggio, Nadja Sachs, Moritz von Scheidt, Julia Hinterdobler, Philipp Müller, Julia Werner, Barbara Stiller, Zouhair Aherrahrou, Jeanette Erdmann, Andrea Zaliani, Mira Graettinger, Jeanette Reinshagen, Sheraz Gul, Philip Gribbon, Lars Maegdefessel, Jürgen Bernhagen, Hendrik B. Sager, Matthias Mann, Heribert Schunkert, Thorsten Kessler
Journal: Circulation Research (2023)

The ADAMTS7 locus was genome-wide significantly associated with coronary artery disease. Lack of the ECM (extracellular matrix) protease ADAMTS-7 (A disintegrin and metalloproteinase-7) was shown to reduce atherosclerotic plaque formation. Here, we sought to identify molecular mechanisms and downstream targets of ADAMTS-7 mediating the risk of atherosclerosis.Targets of ADAMTS-7 were identified by high-resolution mass spectrometry of atherosclerotic plaques from Apoe-/- and Apoe-/-Adamts7-/- mice. ECM proteins were identified using solubility profiling. Putative targets were validated using immunofluorescence, in vitro degradation assays, coimmunoprecipitation, and Förster resonance energy transfer-based protein-protein interaction assays. ADAMTS7 expression was measured in fibrous caps of human carotid artery plaques.In humans, ADAMTS7 expression was higher in caps of unstable as compared to stable carotid plaques. Compared to Apoe-/- mice, atherosclerotic aortas of Apoe-/- mice lacking Adamts-7 (Apoe-/-Adamts7-/-) contained higher protein levels of Timp-1 (tissue inhibitor of metalloprotease-1). In coimmunoprecipitation experiments, the catalytic domain of ADAMTS-7 bound to TIMP-1, which was degraded in the presence of ADAMTS-7 in vitro. ADAMTS-7 reduced the inhibitory capacity of TIMP-1 at its canonical target MMP-9 (matrix metalloprotease-9). As a downstream mechanism, we investigated collagen content in plaques of Apoe-/- and Apoe-/-Adamts7-/- mice after a Western diet. Picrosirius red staining of the aortic root revealed less collagen as a readout of higher MMP-9 activity in Apoe-/- as compared to Apoe-/- Adamts7-/- mice. To facilitate high-throughput screening for ADAMTS-7 inhibitors with the aim of decreasing TIMP-1 degradation, we designed a Förster resonance energy transfer-based assay targeting the ADAMTS-7 catalytic site.ADAMTS-7, which is induced in unstable atherosclerotic plaques, decreases TIMP-1 stability reducing its inhibitory effect on MMP-9, which is known to promote collagen degradation and is likewise associated with coronary artery disease. Disrupting the interaction of ADAMTS-7 and TIMP-1 might be a strategy to increase collagen content and plaque stability for the reduction of atherosclerosis-related events.
Research progress in the molecular mechanism of ferroptosis in Parkinson's disease and regulation by natural plant products
Authors: Kailin Yang, Liuting Zeng, Jinsong Zeng, Ying Deng, Shanshan Wang, Hao Xu, Qi He, Mengxia Yuan, Yanfang Luo, Anqi Ge, Jinwen Ge
Journal: Ageing Research Reviews (2023)
Endothelial cells differentiated from patient dermal fibroblast-derived induced pluripotent stem cells resemble vascular malformations of port-wine birthmark
Authors: Vi Nguyen, Chao Gao, Marcelo L Hochman, Jacob Kravitz, Elliott H Chen, Harold I Friedman, Camilla F Wenceslau, Dongbao Chen, Yunguan Wang, J Stuart Nelson, Anil G Jegga, Wenbin Tan
Journal: British Journal of Dermatology (2023)

Lesional induced pluripotent stem cell-derived endothelial cells can resemble pathological vascular phenotypes of port-wine birthmark (PWB). Our data demonstrate that multiple pathways, including Hippo and Wnt, NFκB, TNF, MAPK and cholesterol metabolism, are dysregulated. These data suggest new therapeutics can be developed to target such dysregulated pathways in the treatment of PWB.
Neoadjuvant Immune Checkpoint Inhibitor Therapy for Localized Deficient Mismatch Repair Colorectal Cancer
Authors: Oluwadunni E. Emiloju, Frank A. Sinicrope
Journal: JAMA Oncology (2023)

Colorectal cancers (CRCs) with deficient DNA mismatch repair (dMMR) account for 15% of all CRCs. Deficient MMR is a predictive biomarker associated with responsiveness to immune checkpoint inhibitors (ICIs) in solid tumors, including CRC. The remarkable effectiveness of ICIs in metastatic CRC has led to their evaluation in the neoadjuvant and adjuvant treatment of localized disease.Multiple prospective phase 2 studies in limited numbers of patients with localized dMMR CRC demonstrate high complete clinical and pathological response rates (60%-100%) to neoadjuvant ICIs, with low rates of grade 3 or higher ICI-related toxic effects. Given the median follow-up of 12 to 25 months in these studies, longer-term monitoring is needed to determine the durability of response and to ensure that oncologic outcomes are not compromised in patients undergoing nonoperative management. Neoadjuvant ICI therapy is especially attractive for patients with rectal cancer given the significant morbidity that accompanies pelvic irradiation and total mesorectal excision. Ongoing and planned prospective phase 2 trials will provide further data on important issues, including optimal neoadjuvant treatment duration, ICI monotherapy vs combination, and the need for adjuvant ICI therapy.While this review found that early results of neoadjuvant immunotherapy for localized dMMR CRC show high rates of major and complete pathological response, longer-term follow-up data are needed to ensure that oncologic outcomes are not compromised and are ideally improved. Neoadjuvant ICI therapy in localized dMMR CRC represents a potential paradigm shift with implications for organ preservation.
Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non–Small Cell Lung Cancer
Authors: Motoko Tachihara, Kayoko Tsujino, Takeaki Ishihara, Hidetoshi Hayashi, Yuki Sato, Takayasu Kurata, Shunichi Sugawara, Yoshimasa Shiraishi, Shunsuke Teraoka, Koichi Azuma, Haruko Daga, Masafumi Yamaguchi, Takeshi Kodaira, Miyako Satouchi, Mototsugu Shimokawa, Nobuyuki Yamamoto, Kazuhiko Nakagawa
Journal: JAMA Oncology (2023)

Administration of durvalumab after concurrent chemoradiotherapy is the standard treatment of unresectable, locally advanced non-small cell lung cancer (NSCLC); however, 20% to 30% of patients do not receive durvalumab because of adverse events (AEs) during concurrent chemoradiotherapy. In addition, radiotherapy and immunotherapy have a synergistic effect.
Increase in bloodstream infections caused by emm1 group A Streptococcus correlates with emergence of toxigenic M1UK, Belgium, May 2022 to August 2023
Authors: Juan Pablo Rodriguez-Ruiz, Qiang Lin, Christine Lammens, Pierre R Smeesters, Stefanie van Kleef-van Koeveringe, Veerle Matheeussen, Surbhi Malhotra-Kumar
Journal: Eurosurveillance (2023)

Many European countries have recently reported upsurges in invasive group A Streptococcus (iGAS) infections, mainly caused by emm1 Streptococcus pyogenes, specifically the toxigenic M1UK lineage. We present the epidemiology of emm1 causing iGAS in Belgium during 2018-August 2023, and describe an emergence of the toxigenic M1UK lineage in Belgium in mid-2022 that was observed as an increase in bloodstream infections caused by emm1 S. pyogenes that continued into 2023.
Early Access to Testosterone Therapy in Transgender and Gender-Diverse Adults Seeking Masculinization
Authors: Brendan J. Nolan, Sav Zwickl, Peter Locke, Jeffrey D. Zajac, Ada S. Cheung
Journal: JAMA Network Open (2023)

Testosterone treatment is a necessary component of care for some transgender and gender-diverse individuals. Observational studies have reported associations between commencement of gender-affirming hormone therapy and improvements in gender dysphoria and depression, but there is a lack of data from randomized clinical trials.To assess the effect of testosterone therapy compared with no treatment on gender dysphoria, depression, and suicidality in transgender and gender-diverse adults seeking masculinization.A 3-month open-label randomized clinical trial was conducted at endocrinology outpatient clinics and primary care clinics specializing in transgender and gender-diverse health in Melbourne, Australia, from November 1, 2021, to July 22, 2022. Participants included transgender and gender-diverse adults aged 18 to 70 years seeking initiation of testosterone therapy.Immediate initiation of testosterone commencement (intervention group) or no treatment (standard care waiting list of 3 months before commencement). This design ensured no individuals would be waiting longer than the time to standard care.The primary outcome was gender dysphoria, as measured by the Gender Preoccupation and Stability Questionnaire. Secondary outcomes included the Patient Health Questionnaire-9 (PHQ-9) to assess depression and the Suicidal Ideation Attributes Scale (SIDAS) to assess suicidality. Questionnaires were undertaken at 0 and 3 months. The evaluable cohort was analyzed.Sixty-four transgender and gender-diverse adults (median [IQR] age, 22.5 [20-27] years) were randomized. Compared with standard care, the intervention group had a decrease in gender dysphoria (mean difference, -7.2 points; 95% CI, -8.3 to -6.1 points; P < .001), a clinically significant decrease in depression (ie, change in score of 5 points on PHQ-9; mean difference, -5.6 points; 95% CI, -6.8 to -4.4 points; P < .001), and a significant decrease in suicidality (mean difference in SIDAS score, -6.5 points; 95% CI, -8.2 to -4.8 points; P < .001). Resolution of suicidality assessed by PHQ-9 item 9 occurred in 11 individuals (52%) with immediate testosterone commencement compared with 1 (5%) receiving standard care (P = .002). Seven individuals reported injection site pain/discomfort and 1 individual reported a transient headache 24 hours following intramuscular administration of testosterone undecanoate. No individual developed polycythemia.In this open-label randomized clinical trial of testosterone therapy in transgender and gender-diverse adults, immediate testosterone compared with no treatment significantly reduced gender dysphoria, depression, and suicidality in transgender and gender-diverse individuals desiring testosterone therapy.ANZCTR Identifier: ACTRN1262100016864.
Biomarker Analysis of Vistusertib Plus Paclitaxel Regimen—Reply
Authors: Gaia Giannone, Iain A. McNeish, Susana Banerjee
Journal: JAMA Oncology (2023)

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Advancing Patient-Centered Outcomes and Equity in Clinical Trials for BCG-Unresponsive Nonmuscle Invasive Bladder Cancer
Authors: Thomas J. Hwang, Benjamin J. Davies, Mark A. Preston
Journal: JAMA Oncology (2023)

This Viewpoint encourages investigators to move beyond FDA guidance toward patient-centered therapies and health equity for BCG-unresponsive bladder cancer.
The management concept of breast cancer with clinically node-negative/imaging node-positive disease
Authors: Zhao Bi, Tong-Yue Ren, Zhao-Peng Zhang, Yong-Sheng Wang
Journal: International Journal of Surgery (2023)

Bi, Zhao MD; Ren, Tong-Yue MD; Zhang, Zhao-Peng MD; Wang, Yong-Sheng PhD Author Information
Modified L-shaped incision technique for supracardiac total anomalous pulmonary venous connection as an alternative to sutureless technique
Authors: Zicong Feng, Qiyu He, Jianhui Yuan, Zheng Dou, Dongdong Wu, Yuze Liu, Lu Rui, Fengpu He, Zhongkai Wu, Shoujun Li
Journal: International Journal of Surgery (2023)

Background: Modified L-shaped incision technique (MLIT) was successfully applied to the repair of supracardiac total anomalous pulmonary venous connection (TAPVC) with promising mid-term outcomes. It is, however, unclear whether or not MLIT could be an alternative to sutureless technique (ST). Methods: All patients (n=141) who underwent MLIT or ST repair for supracardiac TAPVC between June 2009 to June 2022 were included and a propensity score-matched analysis was performed to reduce the heterogeneity. Results: MLIT was performed in 80.9% (114/141), whereas ST was performed in 19.1% (27/141). Patients who underwent MLIT repair had a lower incidence of pulmonary veinous obstruction (PVO)-related reintervention (1.8% vs. 18.5%, P =0.002), and late mortality (2.6% vs. 18.2%, P =0.006). Overall survival at 10 years was 92.5% (87.7%-97.7%) for MLIT and 66.8% (44.4%-100%) for ST ( P =0.012). Freedom from postoperative PVO at 10 years was 89.1% (83.2%-95.5%) for MLIT and 79.9% (65.6%-97.4%) for ST ( P =0.12). Cox proportional hazards regression identified prolonged mechanical ventilation duration, postoperative PVO, respiratory dysfunction and low cardiac output syndrome were associated with postoperative death and PVO-related reintervention. Conclusions: The MLIT strategy is a safe, technologically feasible, and effective approach for supracardiac TAPVC, which is associated with more favourable and promising freedom from death and PVO-related reintervention.
Field Epidemiology and Public Health Microbiology training: capturing the alumni perspectives of the training’s impact
Authors: Justine Schaeffer, Charlotte Christiane Hammer, Iro Evlampidou, Laura Bubba, Zsofia Igloi, Timothée Dub, Annika Wendland, Jane Whelan, Stine Nielsen, Amrish Baidjoe, Alma Tostmann
Journal: Eurosurveillance (2023)

We present the findings from the European Programme for Intervention Epidemiology Training (EPIET) Alumni Network (EAN) Member Survey conducted in October to December 2021. The EAN consists of field epidemiologists (EPIET) and public health microbiologists (European Public Health Microbiology Training Programme (EUPHEM)) who stay connected after their 2-year fellowship. This active alumni network provides opportunities for career development, mentorship, knowledge exchange and sharing of best practices for community members, affiliated professionals and public health organisations in Europe. Overall, 281 of 732 members participated in the survey. Of the 192 European fellowship alumni respondents, 173 (90%) indicated that skills and competencies acquired during their fellowship improved performance in their role compared with their abilities before the fellowship. Reported skills and competencies that could be further strengthened included data management/analysis, communication, mathematical modelling and leadership/team management. The EAN Member Survey provides valuable feedback to the EAN, as well as the fellowship programme offices at the European Centre for Disease Prevention and Control (ECDC) and affiliated field epidemiology programmes. The COVID-19 pandemic was a stark reminder of how essential cross-border collaborations are for continued European health security. Maintaining and increasing the professional, well-trained workforce remains crucial for optimal response to infectious diseases and protection of public health.